Before going further you must understand the difference between age and aging. Age is the number of years you have lived while aging is a process where the health function slowly goes to decline. And over time the body becomes more and more susceptible to chronic diseases. Most people see aging and dying as a related outcome. But in reality, everyone dies of two possible causes, they either die of accidental trauma or they get sick and succumb to some form of chronic disease.
We already stated the causes of aging but is there anything we can do about it?
Yes, you can follow some tips and tricks to slow your aging process significantly and also stay healthier to stay less vulnerable to chronic diseases.
1:Increasing the Effectiveness of Sirtuins Pathways
These are longevity genes and can have a big impact on our body in terms of endurance, heart health, cognitive function, and more importantly how well we age. Since they play a key role in the aging process in our body there are things you can do to boost sirtuins pathways.
We know that calorie restriction will slow aging in many species. Some researches have revealed that molecules that are responsible for slowing the aging process interact with sirtuins. These longevity genes are responsible for creating new mitochondria, stimulate apoptosis or program death cells, autophagy or recycling cells, and several other functions.
Sirtuins can only function in the presence of NAD+ which stands for Nicotinamide Adenine Dinucleotide. It’s a derivative of Nicotinic acid also called Niacin or vitamin B6. It comes in two forms NAD+ and NADH, which is a coenzyme that helps turn nutrients into energy. It also helps in energy production in energy production in mitochondria.
Since NAD is necessary for the normal functioning of sirtuins. It has been also seen that NAD’s are also used by DNA repairing proteins called PARP’s which are mostly found in aged people. Although it is necessary to activate sirtuins and PARPs too much activation can exhaust NAD+ supplies can induce cell death if the damage is too severe.
Too much activation of the PARP can induce overexpression of the P53 protein, which is responsible for the elimination of cancer cells but the more it’s activated the more it accelerates the aging process. As you age the NAD+ levels go down and the sirtuins become less functional. As a result, the body suffers slow mitochondrial function and increased oxidative stress which leads to chronic inflammation, cognitive dysfunction, and a significant increase in free radicals which damages the DNA.
The best possible way to deal with declining NAD+ is by supplementing with NAD precursors. There are several NAD precursors available in the market depending on the level of absorptions and effectiveness. Two of the most effective are NMN or nicotinamide mononucleotide and NR which stands for nicotinamide riboside. There is still an open debate on the effectiveness of both drugs but some studies have shown that NMN has edged out NR in many aspects.
The recommended dosage of both the drug is approximately 250 to 300 mg per day. But some researchers have also suggested taking 1 gram a day.
Another possible way to accelerate the production of sirtuins is by taking resveratrol. It boosts the activity of sirtuins by increasing mitochondrial function in a way similar to calorie restriction. So supplementing resveratrol can also be used to expand the lifespan of the body. You can also consider pterostilbene, which has similar properties to resveratrol and occurs in the same type of plant as Resveratrol. Both of them are strong anti-inflammatories, antioxidants, and show activity to fight off cancer cells. Pterostilbene in some cases has performed better than resveratrol and it stays 7 times longer than resveratrol.
We recommend you not to self-medicate and consult a licensed health professional before taking any sort of medication.
2:Activating AMPK pathways
Activating AMPK pathways will keep your body tissue young and slow aging throughout the body. ATP molecules are broken down and the energy is released in the mitochondria resulting in the production of AMP.
AMPK is an enzyme called that stands for AMP-activated protein kinase. Kinases are simply enzymes that transfer a phosphate group from a high-energy molecule to a specific substrate. AMPK is biochemically activated in increasing levels of AMP and decreasing levels of ATP and when AMPK is activated, cells do not make or store fat but rather burn fat and transport glucose. This results in low fat, low blood sugar, and increased insulin sensitivity.
Activated AMPK also promotes autophagy, mitochondria biogenesis, renewal of cellular components, and stimulate the growth of SIRT1. SIRT1 is one of the sirtuins enzymes which helps in DNA repair. AMPK also inhibits signaling of nuclear actor KappaB pathway which is a pro-inflammatory resulting in chronic inflammation.
Some studies show that AMPK is a suppressor of processes related to biological aging. But with age AMPK declines sharply with age. AMPK activation can be suppressed by inflammation. When calorie intake is higher than it is burned off, AMPK activation is also reduced significantly. The cells decrease their energy-releasing, ATP-generating activities, and shift to energy-storing processes generating new fat deposits and creating excess new glucose molecules.
By boosting AMPK activities your tissues will look young and slow down aging throughout the body. These activities also suppress several chronic diseases associated with old age like cardiovascular diseases, metabolic syndrome, liver diseases, etc.
One of the possible ways to boost AMPK pathways is by calorie restriction to the extent that you might not be able to sustain it. Also, another way is to exercise, by stimulating muscle contraction. Some studies suggest that exercise not only affects positively on AMPK but also suggests that the higher the intensity, the more AMPK is activated.
HIIT or High-intensity interval workout is effective in activating AMPK. Other ways to activate AMPK is by consuming dietary fiber especially glucomannan which is a special type of soluble fiber. Several nutrients like Alpha-lipoic Acid or ALA activate AMPK pathways in muscle tissue and Quercitin can increase AMPK in fat muscle and liver. Fish oil, curcumin, and EGCG from green tea can also activate AMPK. And finally, there’s metformin, which is a prescription drug that is used to treat type 2 diabetes. Significant numbers of researchers including David Sinclair from Yale university take metformin as part of their anti-aging regime.
Although it might be good for anti-aging benefits, it does have some tolerable side effects like stomach upset. Metformin is one of those molecules that can replicate the effects of calorie restriction. And since it’s a prescription drug, you can ask your doctor to get one.
From a physical point of view, we recommend you to exercise strenuously and as from a medication point of view, it’s better to consult a health expert who has experience on the matter.
3:Removing Senescent Cells from the body
As we age more and more cells in our body either stop dividing or start to dysfunctional. Since they are metabolically active, they can have an adverse effect on the surrounding cell, such cells are called senescent cells.
Cellular senescence is one of the interesting research on longevity. The cell cycle starts with a process called mitosis, which means replicated chromosomes separate into two different identical nuclei. In the 1960s two researchers Lenord Hayflick and Paul Moorhead discovered that about 50 divisions later, the normal cell will cease to divide. This tendency was termed as Hayflick Limit.
At the end of every chromosome, there is a cap called telomeres. Each time the cell divides, the chromosome is replicated and a little amount of material is lost every time from the end of telomeres. These erode continuously throughout the life of the cell until they reach the Hayflick limit. They almost disappear and leave the DNA information bare. Since no telomeres are left to protect the DNA information some critical information gets chewed out.
This also makes the DNA vulnerable to damage. Other factors that can shorten telomeres can be stress, smoking, obesity, lack of exercise, and poor nutrition. If the damage to the DNA is severe the cell stop functioning normally and might enter into the state of Apoptosis, which is the programmed death of cells. But in most cases, the cells stop functioning normally instead of dying which is a state of senescent.
Since senescent cells cannot replicate like normal cells, they are still metabolically active. And typically invoke immune response by releasing certain pro-inflammatory substances like cytokines, chemokines, and extracellular matrix proteases. These substances are called SASP (senescence-associated secretory phenotype). Although they are secreted in small quantities the effects of SASP are profound. It can adversely affect the surrounding tissue of the microenvironment, interfering with the normal function of other processes like tissue regeneration and remodeling. This can also lead to chronic inflammation and cancerous tumors.
As we grow older, we accumulate more senescent cells and these cells have a major contribution to the aging process. Researchers have been studying a class of molecules called senolytics, which is selectively induced health in senescent cells and remove SASP. Senescent cells have a pro-survival gene that prevents them from apoptosis and there are two drugs available in the market that can selectively kill senescent cells, first is dasatinib, used to treat in some cases of leukemia and the other is quercetin, a flavonoid antioxidant and plant pigmentation found in deep-colored plants. Both we able to remove senescent cells but were effective in different tissue of the body.
Dasatinib was found effective in removing senescent fat cell progenitors which are biological cells similar to stem cells but are more prone to differentiate into a specific target cell. Quercetin was effective in removing human endothelial cells. It was also found that combining two drugs forms a synergy that was effective at removing some types of senescent cells. Removing as little as 30% of senescent cells was enough to slow aging down.
Not all senescent cells are harmful, they play significant roles in cellular reprogramming and wound healing. So this situation is more like a balance. The role of senolytics is just to clear enough senescent cells to slow down the aging process without disturbing cellular reprogramming or wound healing.
To use Dasatinib you need a prescription since it is used to treat leukemia and it’s expensive. Quercetin on the other hand is easily available in the market and can be supplemented with natural foods like red wine, green tea, kale, blueberries, dark chocolate, etc. it is also anti-inflammatory and natural antihistamine, meaning it promotes healthy liver and skin.
Senolytics is more related to cancer research. And several senolytics are being studied to target cancer-preventing pathways. One of the experimental anti-cancer drugs is Navitoclax. It induces apoptosis in senescent cells, it also works as a protective agent against memory loss in mice genetically engineered to induce Alzheimer’s.
The adverse effects of excess senescent cells can be way out of proportion, exhibiting harmful effects on the surrounding tissue microenvironment. Since most of the drugs are still in an experimental stage or harder to obtain, we can supplement Quercetin in the form of natural food. It is widely available and easily affordable.
4:Keeping mTOR and AMPK pathways in Balance
The term mTOR stands for mechanistic target of Rapamycin. It’s an enzyme that’s encoded by the mTOR gene it is also a kinase, which means these are the enzymes that catalyze the transfer of phosphate group from high energy phosphate.
After an expedition In 1960 in Easter islands, local inhabitants by the name Rapanui have natural products from plants and soil that had possible therapeutic value. In 1972 a soil bacterium was discovered and had a potent anti-fungal activity. It was later called Rapamycin, Rapa to pay homage to the inhabitants Rapa Nui and Mycin for antifungal activities.
Some tests also revealed that Rapamycin had potent immunosuppressive and anti-cancer activity. In 1994 an enzyme “target of rapamycin” was discovered in mammalian tissue. So now this enzyme and the pathway that it activates is called mammalian target of Rapamycin, mTOR pathways.
Whenever there’s plenty of nutrition and calorie available in the body, we will be real active and our muscles will consume a lot of energy. The mitochondria increase the working capacity and ATP production goes up. The cells divide more and we tend to grow and repair. mTOR is the protein senses this condition and turns up the heat. However, when the body goes into calorie restriction condition the mTOR pathways are inhibited.
mTOR pathway includes two distinct complexes mTOR complex -1 and mTOR complex-2. It acts as a central hub for integrating signals from upstream pathways which includes growth factors like IFG-1 and IFG-2, insulin, and amino acids. It also plays a role in sensing cellular nutrients, oxygen, and energy levels. This pathway acts as a molecular switch to regulate cellular growth and proliferation in response to nutrients but all of this growth and higher energy levels come at a price.
Though mTOR produces energy and performance, it also produces junk in the process. And in Autophagy, these junk products are broken down and recycled. But autophagy can only kick in when the mTOR pathway is inhibited. So we can say that the mTOR pathways are great for growth and energy but bad for extending lifespan. To understand with an example, animals that grow very quickly like mice, insects, and worms have a short lifespan, but animals with prolonged growth like elephants and whales have a long life span. However, if you notice within species bigger animals have a shorter lifespan than small ones, for example, big dogs have a shorter lifespan than small ones.
Too much mTOR pathway activation can contribute to a large number of chronic diseases like cancer, obesity, type-2 diabetes, and neurodegeneration. Inhibiting the mTOR pathway improves insulin sensitivity and promotes autophagy.
Another enzyme called APMK stimulates both autophagy and inhibits mTOR. Since rapamycin being a potent antifungal, immunosuppressive and anti-cancer drug, it also inhibits the mTOR pathway and prevents it from activating. Several studies have show rapamycin extends lifespan in mice by 60% another study shows that dogs who took rapamycin also got cardiovascular benefits similar to mice.
Inhibiting the mTOR pathway cannot be all bad, activating to some extent can do good like heal wounds for growing muscle and more energy. As we age we need those things but as we grow older sarcopenia sets in, where the body suffers a loss of muscle mass. So, We need to grow new muscle by including more amounts of protein in our diet.
Taking rapamycin is not an answer, mTOR pathways must be activated sometimes especially in aging adults. We need to cycle between the periods when the mTOR pathway is activated, we are growing tissue, healing and boosting energy production, and periods when the mTOR pathway is inhibited where the process of autophagy is activated and clearing out toxic cellular waste.
Since the primary activating factors kick in the presence of excess amino acid. So you can consider changing your protein intake. We suggest on the day of exercise if you try weight lift exercises take around 6 scoops of protein powder. And on the day of a cardio workout, we recommend you take 2 scoops of protein powder. You can also try the Keto diet to get an adequate amount of protein for better results.
The other way to balance out this situation is by inhibiting of mTOR pathway and achieving autophagy. That can be done by activating AMPK pathways. To activate them consume less amino acid and perform HIIT sessions. Sadly there is no way to measure when mTOR pathways or AMPK pathways are activated. We think you can assume when you are gaining muscle mass and feeling an increase in strength, then mTOR is activated. But when you improve your cardiovascular fitness and mitochondrial health, AMPK is activated. The only way to determine is to check in 10 to 20 years, how your body is holding up.
5:Performing HIIT Training
Performing HIIT training can give you several benefits like weight loss, triggering the EPOC effect, increase in VO2 max, normal blood sugar, normal BP, and increase overall energy. It also increases testosterone, HGH, and nitric oxide levels to improve libido.
HIIT can also have powerful anti-aging properties. It can slow down aging, can expand your health and age lifespan. HIIT mainly focuses on your mitochondrial health. As we know mitochondria are tiny structures that live inside our body cells. Different types of cells can have a different amount of mitochondria. Its function is to generate energy that we need to live and function and they do this by burning sugar in the presence of oxygen in our bloodstream. Mitochondria oxidize that sugar to turn it into ATP. APT cells fuels our muscle, brains, and our organs. A typical adult needs 200 to 300 moles of ATP in a single day. Mitochondria is also responsible for apoptosis or the programmed death of the cells.
Our mitochondrial health is determined by two things, first is how many mitochondria we have and how well each of the mitochondria is functioning. Mitochondria are produced through the process of mitochondrial biogenesis. As we age mitochondrial biogenesis goes in to decline and the amount of mitochondria in our body goes into decline. And the ones we do have, don’t function at peak efficiency. Also, some of them do not function properly and start to malfunction. Mitochondrial dysfunction is the reason behind all chronic diseases. Every organ in our body including the skin ages because of mitochondrial dysfunction.
Human beings have two different ages first is the chronological age meaning number of years we have lived and the biological age that appears based on our looks, cognitive abilities, mobility, and activity level. Mitochondrial health can impact a person’s biological age dramatically.
Mitochondrial health can be improved in three different ways. The first is by increasing the number of mitochondria in the body, improving mitochondrial health, and getting rid of those mitochondria that are not functioning properly. Mitochondria adapt to physical stress by creating more of themselves. Since HIIT triggers mitochondrial biogenesis, it cranks up the production of mitochondria. The only downside to the working of mitochondria is that they make more oxidative reactive species or free radicals.
HIIT training demands significantly high energy levels, to meet that mitochondria respond by regulating the production of ATP. As the production of ATP improves the function of mitochondria improves.
Now to get rid of dysfunctional mitochondria you have to put your body through autophagy. In autophagy, mitochondria that fail to meet the production of ATP are removed and are replaced with new functional mitochondria.
To measure our performance and detect the actual increase in health and function of mitochondria, you can try aerobic exercises and taking a VO2 max test. You might have seen someone wearing a mask hooked up to a system while cycling or running on a treadmill, that’s VO2 max. It measures the maximum amount of oxygen you took while exercising at the absolute peak performance. The more oxygen you consume the better shape you are in. All oxygen consumption happens in mitochondria. Here the oxygen is used to burn off the sugar and relapse ATP.
Improvement in VO2 max test means your body capacity of consuming oxygen is good and the functioning of mitochondria is at its peak. A study revealed that older people who performed HIIT sessions have impressive gains in mitochondria levels. Also, skin biopsies done on them after 3 months training program revealed that their skin got a boost at collagen production and their skin felt more hydrated.
We recommend you to perform at least 4 HIIT sessions in a week and you will feel the difference in just a few months.